The principal objective of this research is to develop an injectable, bioerodible drug delivery device that will release the narcotic antagonist naltrexone by an erosion-controlled process by kinetics that approach zero order. Primarily because of size constraints, the designed lifetime will be 30 days. This system will be developed using an ointment-like bioerodible poly(ortho ester), recently developed in our laboratories. The hydrolysis of this polymer is very well understood, and the ultimate degradation products are the toxicologically benign 1,2,6-hexanetriol and a carboxylic acid. The ointment-like consistency of the polymer allows incorporation of high concentrations of naltrexone by a simple mixing procedures at room temperature without the use of solvents, thus minimizing potentially adverse naltrexone-polymer interactions and maximizing the amount of drug that can be incorporated into the polymer. The actual delivery system will consist of a polymer drug mixture, microencapsulated within a bioerodible, macroporous membrane. This encapsulation will confine the ointment-like material to a fixed geometry, allow administration by means of a conventional hypodermic syringe, and prevent removal by the patient. We have selected an interfacial polycondensation procedure to surround the polymer with a macroporous polyamide membrane produced by the condensation of a diamine and a diacid chloride. The ointment-like material is first mixed with dry ice and then ground to produce a fine powder. This is then added to ethanol, maintained at -40 degrees C, the diamine added, and this mixture dispersed in n- hexane, containing the diacid chloride, also maintained at -40 degrees C. Because polyamides are essentially nondegradable and contain a toxic diamine, a special diamine prepared from L-alpha-alanine and a diol will be prepared. This diamine is degradable by virtue of the ester groups and is based on a nontoxic amine. The resulting 90 micromoles capsules can be injected through an 18-gauge needle. Toxicology and pharmacokinetic data will be obtained to show biocompatibility and functionality of the system. The specific studies proposed are mutagenicity testing, an intravenous biodeposition study with polymer hydrolysate in rats, a tissue biocompatibility in rabbits, and a pharmacokinetic study in rabbits.